The underlying premise is that respiration can only be understood in the context of the interplay among controlled elements, the controller, and the nonrespiratory influences on both the controller and the controlled element, seen as an integrated system. Each element of the system contributes to the modulation of ventilation in the normal resting state, but the relative importance of these components may change under conditions of environmental stress or disease. This program consist of seven projects. Project 1 deals with the central factors that coordinate respiratory skeletal muscle function (Project 1A) and the medullary mechanisms concerned with integration and coordination of respiratory and cardiovascular responses (Project 1B). Project 2 evaluates the behavioral aspects of respiratory control and the relationship between the conscious perceptions of respiratory sensation to dyspnea and respiratory motor responses. Project 3 assesses the neuromuscular regulation of breathing in infants with emphasis on the function of upper airway muscles. Project 4 investigates breathing during sleep in adults. The focus of Project 4A is the functional responses of the upper airway muscles and their interrelationship with the geometry and dynamic mechanical properties of the upper airway; while Project 4B studies the mechanisms that produce and terminate recurrent apneas and periodic breathing. The emphasis of Project 5 is on the regulation of respiratory muscle blood flow and its role in adaptation to stress. Project 6 deals with the neural control of the respiratory muscles and how it is related to the cellular mechanisms that affect airway responses. The central regulation of airway smooth muscle activity is the focus of Project 6A; thermal factors acting reflexly and directly on the airway are studied in Project 6B; while Project 6C examines the effect of the intrinsic cellular characteristics of smooth muscle on airway responsivity. Project 7 explores the mechanisms which control the reactions of the lung to injury and their possible implications in the control of breathing. Basic data will be obtained on the organization and operation of the respiratory controller and its interaction with other control systems. Additionally, the studies have been designed to identify mechanisms and risk factors at the system and cellular level for respiratory failure which will be useful in devising and evaluating therapeutic interventions.